Delivery of cardiovascular progenitors with biomimetic microcarriers reduces adverse ventricular remodeling in a rat model of chronic myocardial infarction.

Despite tremendous progress in cell-based therapies for heart repair, many challenges still exist. To enhance the therapeutic potential of cell therapy one approach is the combination of cells with biomaterial delivery vehicles. Here, we developed a biomimetic and biodegradable micro-platform based on polymeric microparticles (MPs) capable of maximizing the therapeutic potential of cardiac progenitor cells (CPCs) and explored its efficacy in a rat model of chronic myocardial infarction. The transplantation of CPCs adhered to MPs within the infarcted myocardial microenvironment improved the long-term engraftment of transplanted cells for up to one month. Furthermore, the enhancement of cardiac cellular retention correlated with an increase in functional recovery. In consonance, better tissue remodeling and vasculogenesis were observed in the animals treated with cells attached to MPs, which presented smaller infarct size, thicker right ventricular free wall, fewer deposition of periostin and greater density of vessels than animals treated with CPCs alone. Finally, we were able to show that part of this beneficial effect was mediated by CPC-derived extracellular vesicles (EVs). Taken together, these findings indicate that the biomimetic microcarriers support stem cell survival and increase cardiac function in chronic myocardial infarction through modulation of cardiac remodeling, vasculogenesis and CPCs-EVs mediated therapeutic effects. The biomimetic microcarriers provide a solution for biomaterial-assisted CPC delivery to the heart. STATEMENT OF SIGNIFICANCE: In this study, we evaluate the possibility of using a biomimetic and biodegradable micro-platform to improve cardiovascular progenitor therapy. The strategy reported herein serves as an injectable scaffold for adherent cells due to their excellent injectability through cardiac catheters, capacity for biomimetic three-dimensional stem cell support and controllable biodegradability. In a rat model of chronic myocardial infarction, the biomimetic microcarriers improved cardiac function, reduced chronic cardiac remodeling and increased vasculogenesis through the paracrine signaling of CPCs. We have also shown that extracellular vesicles derived from CPCs cultured on biomimetic substrates display antifibrotic effects, playing an important role in the therapeutic effects of our tissue-engineered approach. Therefore, biomimetic microcarriers represent a promising and effective strategy for biomaterial-assisted CPC delivery to the heart.

On the microscopic origins of relaxation processes in aqueous peptide solutions undergoing a glass transition.

We combine broadband dielectric spectroscopy (BDS) with 1H and 2H nuclear magnetic resonance (NMR) to study molecular dynamics in mixtures of ε-polylysine with H2O or D2O. In BDS, four relaxation processes can be attributed to molecular dynamics. While the fastest process P1 obeys the Arrhenius law, the slowest process P4 shows prominent non-Arrhenius behavior typical of structural α relaxation. For the intermediate processes P2 and P3, the temperature dependence changes at the glass transition temperature Tg. The 1H and 2H NMR results yield insights into the molecular origins of these relaxation phenomena. In these NMR analyses, we exploit, in addition to the isotope selectivity of the method, the possibility to distinguish between various types of motion based on their respective line-shape effects and the capability to single out specific molecular moieties based on different spin-lattice relaxation behaviors. In this way, we reveal that process P1 results from the rotation of side and end groups of the peptide, while process P2 is caused by a reorientation of essentially all water molecules, which are quasi-isotropic and survive well below Tg. As for the peptide backbone dynamics, we find evidence that rotational motion of polar groups is involved in process P3 and that nonpolar regions show a dynamical process, which is located between P3 and P4. Thus, the NMR analyses do not yield evidence for coexisting fast peptide-decoupled and slow peptide-coupled water species, which contribute to BDS processes P2 and P3, respectively, but minor bimodality of water motion may remain undetected. Finally, it is demonstrated that the proton/deuteron exchange needs to be considered when interpreting experimental results for molecular dynamics in aqueous peptide solutions.

Use of semisynthetic dura mater substitute as a patch graft for prosthesis extrusion in anophthalmic socket. / Uso de sustituto semisintético de duramadre como injerto tras extrusión de prótesis en una cavidad anoftálmica.

We present a case report of a three-year old patient diagnosed with retinoblastoma in her left eye. The course of the disease made enucleation of the latter eye and a prosthesis implant necessary. Two years after surgery, partial prosthesis extrusion occurred and a semisynthetic dura mater substitute was used as a patch graft to cover the defect. To our knowledge, semisynthetic dura mater substitutes' use in this scenario has not been previously reported.

Tuning molecular dynamics by hydration and confinement: antiplasticizing effect of water in hydrated prilocaine nanoclusters.

In glass-forming substances, the addition of water tends to produce the effect of lowering the glass transition temperature, Tg. In a previous work by some of us (Ruiz et al., Sci. Rep., 2017, 7, 7470) we reported on a rare anti-plasticizing effect of water on the molecular dynamics of a simple molecular system, the pharmaceutically active prilocaine molecule, for which the addition of water leads to an increase of Tg. In the present work, we study pure and hydrated prilocaine confined in 0.5 nm and 1 nm pore size molecular sieves, and carry out a comparison with the bulk compounds in order to gain a better understanding of the microscopic mechanisms that result in this rare effect. We find that the Tg of the drug under nanometric confinement can be lower than the bulk value by as much as 17 K. Through the concurrent use of differential scanning calorimetry and broadband dielectric spectroscopy we are able to observe the antiplasticizing effect of water in prilocaine also under nanometric confinement, finding an increase of Tg of up to almost 6 K upon hydration. The extension of our analysis to nanoconfined systems provides a plausible explanation for the very uncommon antiplasticizing effect, based on the formation of water-prilocaine molecular complexes. Moreover, this study deepens the understanding of the behavior of drugs under confinement, which is of relevance not only from a fundamental point of view, but also for practical applications such as drug delivery.

Natural disaster management: experience of an academic institution after a 7.8 magnitude earthquake in Ecuador.

OBJECTIVES: This case study describes the implementation of an academic institution's disaster management plan. STUDY DESIGN: Case study. METHODS: USFQ's Medical School developed a six-phase disaster relief plan consisting of: induction, establishing a base camp, crisis management and mental health aid, creation of multidisciplinary teams and multi-agency teams, and reconstruction. Each phase uses a community-oriented approach to foster survivor autonomy and recovery. RESULTS: Our methodology facilitated the successful implementation of multidisciplinary interventions to manage the earthquake's aftermath on the personal, community and regional levels, treated and prevented psychological and physical morbidity among survivors and promoted healthy living conditions and independence. CONCLUSIONS: A multidisciplinary response team that addresses medical needs, mental health, education, food, nutrition and sanitation is highly effective in contributing to timely, effective relief efforts. The short- and long-term solutions we describe could be applicable to other academic centres' interventions in future disaster scenarios around the world.

Qualitative analysis of repaired filtering blebs with anterior segment-optical coherence tomography. / Análisis cualitativo de ampollas de filtración reparadas mediante tomografía de coherencia óptica de segmento anterior.

OBJECTIVE: To provide a qualitative analysis of filtering blebs after being surgically repaired due to late blebs leaks. METHODS: Blebs were studied 6 months after surgical reparation using AS-OCT Triton (Topcon®). An analysis was made of the morphological pattern and internal structures of blebs, including the covering, in 10 patients. The images were obtained using OCTs at a wavelength of 1050nm. RESULTS: According to the Hirooka classification, three different patterns were found in the structure of blebs, which made it possible to correlate them with their functionality. A full covering was observed in 70% of the cases, and they showed sub-epithelial cysts (cystoid pattern). Two cases showed a full conjunctival retraction without Tenon's covering. The walls were thin, with a de-structured bleb (diffuse pattern) being visualised. In the third group, the image showed a partial conjunctival retraction with Tenon's covering. There were some sub-epithelial diffuse cysts with walls following a laminar pattern. CONCLUSION: Using AS-OCT, it is possible to study the bleb's characteristics in detail, as well as the cover, in the case of blebs requiring repair due to late leaks, using conjunctival advancement. It allows for the early visualisation of conjunctival retractions that were not visible in a slit lamp, and to predict the functionality of the blebs by their morphology.

Analysis and follow-up of type 1 choroidal neovascularisation with optical coherence tomography-angiography after antiangiogenic treatment. / Análisis y seguimiento con angiografía por tomografía de coherencia óptica de neovascularización coroidea tipo 1 en degeneración macular tras tratamiento antiangiogénico.

AIM: To describe the characteristics of type 1 choroidal neovascularisation (CNV) in age-related macular degeneration (ARMD) using two different optical coherence tomography angiography (OCT-A) devices sequentially during a standard protocol of three intravitreal injections of an anti-vascular endothelial growth factor (anti-VEGF). METHODS: The study included 6 eyes with naïve neovascular ARMD. Macular OCT-A images were acquired using AngioPlex Cirrus HD-OCT 5000 (Carl Zeiss Meditec, Inc., Dublin, USA) and DRI OCT Triton SS-OCT Angio (Topcon, Medical Systems, Inc. Oakland, NJ, USA). The macular OCT-A scan covered an area of 3×3mm. Distinct morphological patterns and quantifiable features of the neovascular membranes were studied on en face projection images, which were taken at different stages of the follow-up. RESULTS: Treatment response could be estimated using the OCT-A criteria of CNV activity. Higher activity scores before treatment resulted in a greater decrease in the membrane area. The estimated net decline in area ranged from 83.5% to 1.4%. The OCT-A performed one-week after treatment revealed the greatest area reductions. CONCLUSIONS: OCT-A provides new possibilities for the non-invasive assessment of features of neovascular networks and CNV structural morphology. Newly described activity criteria can also guide therapeutic decisions, and help in evaluating responses. Quantitative and qualitative information can be provided with this technique. However, further software development and future investigation are essential to define the role of this tool on a daily basis.

Relationships between airborne pollen grains, wind direction and land cover using GIS and circular statistics.

Airborne bio-aerosol content (mainly pollen and spores) depends on the surrounding vegetation and weather conditions, particularly wind direction. In order to understand this issue, maps of the main land cover in influence areas of 10km in radius surrounding pollen traps were created. Atmospheric content of the most abundant 14 pollen types was analysed in relation to the predominant wind directions measured in three localities of SW of Iberian Peninsula, from March 2011 to March 2014. Three Hirst type traps were used for aerobiological monitoring. The surface area for each land cover category was calculated and wind direction analysis was approached by using circular statistics. This method could be helpful for estimating the potential risk of exposure to various pollen types. Thus, the main land cover was different for each monitoring location, being irrigated crops, pastures and hardwood forests the main categories among 11 types described. Comparison of the pollen content with the predominant winds and land cover shows that the atmospheric pollen concentration is related to some source areas identified in the inventory. The study found that some pollen types (e.g. Plantago, Fraxinus-Phillyrea, Alnus) come from local sources but other pollen types (e.g. Quercus) are mostly coming from longer distances. As main conclusions, airborne particle concentrations can be effectively split by addressing wind with circular statistics. By combining circular statistics and GIS method with aerobiological data, we have created a useful tool for understanding pollen origin. Some pollen loads can be explained by immediate surrounding landscape and observed wind patterns for most of the time. However, other factors like medium or long-distance transport or even pollen trap location within a city, may occasionally affect the pollen load recorded using an air sampler.

Papillophlebitis versus paediatric venous thrombosis. A case with 46C/T polymorphism in the F12 coagulation gene. / Papiloflebitis versus trombosis venosa pediátrica. Un caso con polimorfismo C46T del gen F12 de la coagulación.

CLINICAL CASE: An 8 year-old boy with no known diseases, with sudden loss of visual acuity (VA) in the left eye (LE). EXAMINATION: VA 1 in right eye, and 0.1 in LE, discrete left relative afferent pupil defect (RAPD). Normal biomicroscopy. Funduscopy: congestive papilla, venous tortuosity, peripapillary haemorrhages with macular oedema in LE. The systemic study only revealed A C46Tpolymorphism in the F12 coagulation gene. He had a VA of 1 and normal funduscopy 8 months later. DISCUSSION: Papillophlebitis is an inflammatory and non-ischaemic central retinal vein occlusion, ophthalmoscopically similar to central retinal vein thrombosis. The systemic study is essential to rule out underlying diseases.

Linkage analysis and detection of somatic, postzygous RB1 mutations in Serbian retinoblastoma patients.

PURPOSE: The etiology of retinoblastoma (RB) is mutational inactivation of two RB1 alleles, the prototype of tumor suppressor gene. The aim of this research was to reveal sporadic, postzygous RB1 gene mutations, in particular loss of heterozygosity (LOH), from formalin-fixed, paraffin-embedded tumor samples in RB patients, as well as tracking RB1 allele inheritance in 10 RB families. METHODS: The mutational studies were carried out in the peripheral blood lymphocytes' DNA of 4 bilateral and 12 unilateral RB patients and DNAs from tumors from 3 bilateral and 10 unilateral patients. Tumor samples were collected from the same patients whose blood was analyzed. DNA was extracted and linkage analysis and microsatellite markers method were performed. LOH for two RB1 intragenic markers was analyzed. RESULTS: Ten LOH were found in the area of two intragene microsatellite loci. Linkage analysis revealed inheritance of RB1 alleles in 10 families. LOH was found in 63.16% of tumors. CONCLUSION: Peripheral blood lymphocytes' DNA gives better results as a control group for somatic mutations than DNA isolated from eye tissue outside the tumor. Linkage analysis is essential for identifying the individual risk, offering the possibility of an adequate genetic counseling in familial RB.

General trends in airborne pollen production and pollination periods at a Mediterranean site (Badajoz, southwest Spain).

BACKGROUND: The aim of this study was to determine trends in the airborne pollen concentration and pollination period for the principal sources of pollen in Badajoz (southwest Spain) over 15 years of monitoring (1994-2008). METHODS: Airborne pollen was monitored by continuous sampling with a Hirst volumetric sampler. Pollen trends were investigated by linear regression and correlation analysis using mean annual and monthly pollen concentrations. The aerobiological results were compared with meteorological data (temperature and rainfall). RESULTS: During the study period, the mean total annual rainfall was 66.2 mm lower than normal and the mean annual temperature 0.8 degrees C higher than normal. No temporal trend was found for total airborne pollen concentration, but differences were observed for monthly data, namely, an increase in January, February, and May and a decrease in March and June. For the different pollen types studied, there was a general trend toward increased values in the month with the highest values, and this trend seemed to be related to temperature.The beginning of the main pollen season occurred later, and the end occurred sooner; therefore, the main pollen season seems to be shorter. CONCLUSIONS: Our data reflect trends in the response of plants to changing rainfall stress patterns in Mediterranean countries, and these trends seem to be different from those of temperate countries. Nonetheless, a longer study period will be required to confirm these preliminary conclusions.

Coronary artery perforations in the contemporary interventional era.

BACKGROUND: Coronary perforations represent a serious complication of percutaneous coronary intervention (PCI). METHODS: We performed a retrospective analysis of documented coronary perforations at Massachusetts General Hospital from 2000 to 2008. Medical records review and detailed angiographic analysis were performed in all patients. RESULTS: Sixty-eight cases of coronary perforation were identified from a total of 14,281 PCIs from March 2000 to March 2008 representing an overall incidence of 0.48%. The study cohort was predominantly male (61.8%), mean age 71+/-11 years with 78% representing acute cases (unstable angina: 36.8%, NSTEMI: 30.9%, STEMI: 10.3%). Coronary artery perforation occurred as a complication of wire manipulation in 45 patients (66.2%) with 88.9% of this group being hydrophilic wires, of coronary stenting in 11 (16.2%), of angioplasty alone in 6 (8.8%), and of rotational atherectomy in 8 (11.8%). The perforation was sealed with an angioplasty balloon alone in 16 patients (23.5%), and with stents in 14 patients (20.6%) (covered stents: 11.8% and noncovered stents: 8.8%). Emergency CABG was performed in 2 patients (2.9%). Five patients (7.4%) developed periprocedural MI. The in-hospital mortality rate was 5.9% in the study cohort. CONCLUSION: Coronary artery perforation as a complication of PCI is still rare as demonstrated in our series with an incidence of 0.48%. The predominant cause of coronary perforations in the current era of PCI is wire injury.

Impact of drug-eluting stent selection on long-term clinical outcomes in patients treated for unprotected left main coronary artery disease: the sirolimus vs paclitaxel drug-eluting stent for left main registry (SP-DELFT).

AIM: To compare the long-term relative efficacy and safety of SES and PES in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery (ULMCA) disease and to evaluate the role of lesion location and stenting technique in determining outcomes. METHODS AND RESULTS: From April 2002 to April 2004, 288 consecutive patients who underwent elective PCI with DES implantation for de novo lesions on ULMCA have been retrospectively selected and analyzed in seven European and US tertiary care centers. All patients had a minimum follow-up of 3 years. SES was used in 152 patients while 136 received PES. Isolated ostial-shaft disease was present in 27% of patients. Distal LM disease (73%) was treated with single and double stent approach in 29.5% and 43.4% of patients respectively. After 3 years, rates of survival free from any of the events investigated, were independent from lesion location and stenting approach and did not differ significantly between SES and PES groups. Freedom from MACE (SES vs. PES) was 76.3% vs. 83.1% in the ostial/shaft group, 80.3% vs. 72.8% in the distal-single stent group and 67.1% vs. 66.2% in the distal-double stent group. Definite stent thrombosis occurred only in 1(0.3%) patient at 439 days. CONCLUSIONS: In elective patients who underwent PCI for de novo lesions in the ostium, shaft or distal ULMCA, long-term clinical outcomes with SES and PES use were similar independently of lesion location and stenting technique.

Correlation between arthroscopic and histopathological grading systems of articular cartilage lesions in knee osteoarthritis.

PURPOSE: Arthroscopic and particularly histopathological assessments have been used to evaluate alterations of knee cartilage in osteoarthritis (OA). The aim of this study was to examine the correlation between an arthroscopic method to grade the severity of chondropathies and the histological/histochemical grading system (HHGS) applied to the corresponding articular cartilage areas in knee OA. METHODS: The articular cartilage surface was examined by chondroscopy using the Beguin and Locker severity criteria, analysing the lesions in 72 chondroscopic areas. Afterwards, samples were obtained by dividing the cartilage surface of the medial tibiofemoral compartment of three OA knee joints into equal squares and they were evaluated histologically using the HHGS. The correlation between both grading methods was assessed using the weighted Kappa coefficient (K(w)). RESULTS: The results obtained with both scores showed good agreement (K(w): mean+/-standard deviation, 0.619+/-0.071). While the average HHGS scores of the chondral samples showed a better agreement with arthroscopic grades 0, I and II, the arthroscopic evaluation has a tendency to overestimate chondral lesions for histological grades III and IV. The intra- and inter-observer reliability of the HHGS evaluation of chondral lesions was excellent (Intraclass Correlation Coefficient: 0.909 and 0.941, respectively). CONCLUSION: In this study, we found a good quantitative correlation between established arthroscopic severity and histopathological scoring systems, particularly in less advanced lesions. Our results suggest that the arthroscopic method is a valuable tool in clinical research to score chondropathies in the medial femorotibial compartment of the OA knee, although some limitations should not be overlooked.

Pathological effects of alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

BACKGROUND: The pathological effects and the mechanisms of action of intracoronary administration of ethanol for alcohol septal ablation (ASA) for the management of hypertrophic obstructive cardiomyopathy (HOCM) are unknown. METHODS: We examined surgical specimens and, in one case, autopsy specimens from four patients who underwent surgical septal myectomy 2 days to 14 months after unsuccessful ASA. RESULTS: Pathological examination early after ASA showed coagulative necrosis of both the myocardium and the septal perforator arteries. Affected arteries were distended and occluded by necrotic intraluminal debris, without platelet-fibrin thrombi. Late after unsuccessful ASA, excised septal tissue was heterogeneous, containing a region of dense scar, and adjacent tissue containing viable myocytes and interspersed scar. CONCLUSIONS: Intracoronary administration of ethanol in patients with HOCM causes acute myocardial infarction with vascular necrosis. The coagulative necrosis of the arteries, their distension by necrotic debris and the absence of platelet-fibrin thrombi distinguish ethanol-induced infarction from that caused by atherosclerotic coronary artery disease. The direct vascular toxicity of ethanol may be an important aspect of the mechanism of successful ASA.

Differences in the spatial distribution of airborne pollen concentrations at different urban locations within a city.

BACKGROUND: The objective of the present work was to compare pollen counts at three different urban locations within a city to each other and to the counts from a fixed trap. This information could be useful to delimit zones in the urbanized part of the city according to the risk of allergic affections. METHODS: Aerobiological sampling using portable traps was carried out at three points in urban zones of the city of Badajoz (SW Spain) over one year at the same time as continuous sampling using a fixed trap at a point in the nonurban outskirts of the city. The sources of airborne pollen were studied by counting the trees in the streets and squares of the selected zones. A statistical analysis was performed of the differences between the portable and fixed traps and of the temporal and spatial variation in the city as a function of the distribution of the most important pollen sources. RESULTS: Forty-eight pollen types were identified with the fixed trap, and 28 with the portable traps. The grass, olive, and oak pollens come from almost exclusively external sources, there being no spatial differences in their concentrations in the city. Cypress pollen concentrations were much higher at the urban locations than at the fixed trap site. Plane tree pollen levels could be locally very high, reflecting the proximity of the source. Except for ornamental plants, pollen levels were lower at the urban locations than at the site on the outskirts of the city. CONCLUSIONS: (1) Using portable traps at different urban zones in a city could provide information about the spatial variation of atmospheric pollen levels. (2) A knowledge of the often widely variable distribution of ornamental plants with potentially allergenic pollen could be useful in indicating city zones with a greater or lesser incidence of potential pollinosis.